Pharmacologic Category

Antineoplastic Agent, Podophyllotoxin Derivative

Antineoplastic Agent, Topoisomerase II Inhibitor

Pharmacology

Teniposide does not inhibit microtubular assembly; it has been shown to delay transit of cells through the S phase and arrest cells in late S or early G2 phase, preventing cells from entering mitosis. Teniposide is a topoisomerase II inhibitor, and appears to cause DNA strand breaks by inhibition of strand-passing and DNA ligase action.

Use: Labeled Indications

Off Label Uses

Acute lymphoblastic leukemia (adults)

Data from a clinical trial in patients with acute lymphoblastic leukemia (ALL) supports the use of teniposide as consolidation therapy in adults with ALL, in combination with other chemotherapy agents [Linker 1991]. Additional trials may be necessary to further define the role of teniposide in this condition.

Contraindications

Hypersensitivity to teniposide, polyoxyl 35/polyoxyethylated castor oil (Cremophor EL), or any component of the formulation

Dosing: Adult

Note: Patients with Down syndrome and leukemia may be more sensitive to the myelosuppressive effects; administer the first course at half the usual dose and adjust dose in subsequent cycles upward based on degree of toxicities (myelosuppression and mucositis) in the previous course(s).

Dosing: Pediatric

Note: Patients with Down syndrome and leukemia may be more sensitive to the myelosuppressive effects; administer the first course at half the usual dose and adjust dose in subsequent cycles upward based on degree of toxicities (myelosuppression and mucositis) in the previous course(s).

Dosing: Renal Impairment

There are no specific dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment may be necessary in patients with significant renal impairment.

Dosing: Hepatic Impairment

There are no specific dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment may be necessary in patients with significant hepatic impairment.

Reconstitution

Precipitation may occur at any concentration. Teniposide must be diluted with either D5W or NS solutions to a final concentration of 0.1, 0.2, 0.4, or 1 mg/mL. Solutions should be prepared in non-DEHP-containing containers such as glass or polyolefin containers. The use of polyvinyl chloride (PVC) containers is not recommended. Because precipitation may occur at any concentration, the manufacturer recommends administrating as soon as possible after preparation. Teniposide contains N,N-dimethylacetamide, which is incompatible with many closed system transfer devices (CSTDs); the plastic components of CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]).

Administration

IV; must be administered slowly (over at least 30-60 minutes); do not administer by rapid IV injection. Administer through non-DEHP-containing administration sets. Incompatible with heparin; flush infusion line with D5W or NS before and after infusion. Precipitation may occur at any concentration; administer as soon as possible after preparation; inspect solution prior to administration. Observe patient continuously for at least the first 60 minutes after the start of the infusion, observe frequently thereafter. Stop infusion for signs of anaphylaxis (may require treatment with epinephrine, corticosteroids, antihistamines, pressors, or volume expanders); discontinue for clinically significant hypotension during infusion; if infusion is restarted after being withheld for hypotension, reinitiate at a slower infusion rate.

Teniposide contains N, N-dimethylacetamide, which is incompatible with many closed system transfer devices (CSTDs); the plastic components of CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]).

Storage

Store ampuls in refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light. Solutions diluted for infusion in D5W or NS to a concentration of 0.1, 0.2, or 0.4 mg/mL are stable at room temperature for up to 24 hours after preparation; solutions diluted to 1 mg/mL should be used within 4 hours of preparation. Because precipitation may occur at any concentration, the manufacturer recommends administrating as soon as possible after preparation. Use appropriate precautions for handling and disposal. Do not refrigerate solutions prepared for infusion.

Drug Interactions

Barbiturates: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosphenytoin: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with phenytoin and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phenytoin: May decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with phenytoin and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Consider therapy modification

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

ALERT: U.S. Boxed Warning

Experienced physician:

Teniposide is a cytotoxic drug. Administer under the supervision of a qualified health care provider experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.

Bone marrow suppression:

Severe myelosuppression with resulting infection or bleeding may occur.

Hypersensitivity reactions:

Hypersensitivity reactions, including anaphylaxis-like symptoms, may occur with initial dosing or with repeated exposure to teniposide. Epinephrine, with or without corticosteroids and antihistamines, has been employed to alleviate hypersensitivity reaction symptoms.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Severe myelosuppression resulting in infection or bleeding may occur; may be dose-limiting; monitor blood counts during and after treatment.

• Hypersensitivity reactions: [US Boxed Warning]: Hypersensitivity reactions, including anaphylaxis-like reactions, have been reported; may occur with initial dosing or with repeated exposure to teniposide. Epinephrine, with or without corticosteroids and antihistamines, has been employed to alleviate hypersensitivity reaction symptoms. Hypersensitivity reactions may include bronchospasm, dyspnea, hypertension, hypotension, tachycardia, flushing, chills, fever, or urticaria. Monitor closely during infusion (observe continuously for first 60 minutes, frequently thereafter). Stop infusion for signs of anaphylaxis; immediate treatment for anaphylactic reaction should be available during administration (may require treatment with epinephrine, corticosteroids, antihistamines, pressors, or volume expanders). Patients experiencing prior hypersensitivity are at risk for recurrence; re-treat only if the potential benefit outweighs the risk of hypersensitivity; premedication (with corticosteroids and antihistamines) is recommended for re-treatment.

• Hypotension: Hypotension may occur with rapid infusion; infuse slowly over at least 30 to 60 minutes; discontinue for clinically significant hypotension. If infusion is restarted after being withheld for hypotension, reinitiate at a slower infusion rate.

• Toxicity with high doses: Acute CNS depression, hypotension and metabolic acidosis have been reported; these events occurred in patients who received high-dose teniposide (investigation protocol) and were premedicated with antiemetics, which along with the alcohol content of teniposide, may have contributed to the CNS depression.

Disease-related concerns:

• Hepatic impairment: Use with caution; may require dosage reduction in patients with significant impairment.

• Renal impairment: Use with caution; may require dosage reduction in patients with significant impairment.

• Dimethylacetamide (DMA): Teniposide contains N,N-dimethylacetamide, which is incompatible with many closed system transfer devices (CSTDs); the plastic components of CSTDs may dissolve and result in subsequent leakage and potential infusion of dissolved plastic into the patient (ISMP [Smetzer 2015]).

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.